We plan to continue our studies on the pathophysiology of the arterial wall, and its interaction with platelets, as follows: (1) Determine whether the aorta of the aging rat develops patches of increased permeability and cellular infiltration, such as have been observed in larger mammals and interpreted as evidence of early atherosclerosis. (2) Find out whether patches of "early injury" can be produced in the rat by minimal alterations of aortic flow (turbulent flow). These lesions will be studied by transmission and by scanning electron microscopy. Permeability changes will be studied with the aid of tracers, particularly ferritin. (3) Study the effect of platelet masses on the endothelium, by injecting collagen intravenously (in the rat) and thereby inducing platelet aggregates that will lodge in the pulmonary arteries. We will then study the effect of these platelet clumps on the underlying endothelium. (4) Study the effect of platelet masses on the surrounding tissues by preparing pellets of pure rat platelets, and implanting them subcutaneously. The effect of such pellets will be compared with those of pellets of various organ homogenates (heart, kidney, brain). (5) Study large arteries of the dogs - by light and electron microscopy - after two surgical procedures: double ligation, and banding (sheathing). (6) Study the incidence of "stomata" and "stigmata" in the endothelium of arteries and veins after varying periods of occlusion.